Brain-Derived Neurotrophic Factor Regulation of Retinal Growth Cone Filopodial Dynamics Is Mediated through Actin Depolymerizing Factor/Cofilin

• Published in: The Journal of neuroscience Vol. 24; no. 47; pp. 10741 - 10749
• Main Authors: Gehler, Scott, Shaw, Alisa E, Sarmiere, Patrick D, Bamburg, James R, Letourneau, Paul C
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 24.11.2004; Society for Neuroscience
• Subjects: 14-3-3 Proteins - physiology; Actin Depolymerizing Factors; Animals; Brain-Derived Neurotrophic Factor - antagonists & inhibitors; Brain-Derived Neurotrophic Factor - physiology; Chick Embryo; Destrin; Development/Plasticity/Repair; Growth Cones - physiology; Growth Cones - ultrastructure; Heterocyclic Compounds, 4 or More Rings - pharmacology; Intracellular Signaling Peptides and Proteins; Microfilament Proteins - metabolism; Microfilament Proteins - physiology; Myosin Type II - antagonists & inhibitors; Myosin Type II - physiology; Phosphorylation; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - physiology; Pseudopodia - physiology; Retina - ultrastructure; rho-Associated Kinases; Signal Transduction - physiology; Tissue Culture Techniques
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2836-04.2004

The molecular mechanisms by which neurotrophins regulate growth cone motility are not well understood. This study investigated the signaling involved in transducing BDNF-induced increases of filopodial dynamics. Our results indicate that BDNF regulates filopodial length and number through a Rho kinase-dependent mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is necessary and sufficient to transduce the effects of BDNF. Our data indicate that activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics, whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF promotes the activation of ADF/cofilin by reducing the phosphorylation of ADF/cofilin. Although inhibition of myosin II also enhances filopodial length, our results indicate that BDNF signaling is independent of myosin II activity and that the two pathways result in additive effects on filopodial length. Thus, filopodial extension is regulated by at least two independent mechanisms. The BDNF-dependent pathway works via regulation of ADF/cofilin, independently of myosin II activity.